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PACT Centre Pages - CARDIOVASCULAR PRESCRIBING

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Trends in Prescribing of Cardiovascular drugs (Chart 1)

This edition of the PACT Centre Pages focuses on the first two chapters of the National Service Framework for Coronary Heart Disease (NSF for CHD): Reducing Heart Disease in the Population and Preventing CHD in High Risk Patients. It discusses changes in prescribing patterns since the introduction of the NSF and identifies where new evidence from clinical trials may influence future prescribing. Over the last five years prescriptions for the most commonly used cardiovascular drug groups have increased with a corresponding rise in cost (charts 1 and 2). Implementation of the NSF has accelerated growth for drugs used to prevent CHD in the last two years. These increases, particularly for lipid regulating drugs, drugs affecting the renin angiotensin system and calcium channel blockers, are major factors in the growth of the national drugs bill.

Chapter 1 of the NSF is about preventing CHD at the population level by reducing exposure to unnecessary risks. It identifies 4 key interventions: reducing smoking, promoting healthy eating, promoting physical activity and reducing overweight and obesity. Evidence from observational studies supports these interventions¹ but unanswered questions remain about the types of exercise and diet that are of most benefit. Standard 2 of the NSF emphasises reducing the prevalence of smoking. Every health authority had established a smoking cessation service by 2000/01. From April to September 2001, 104,800 people set a quit date through these services. At the 4-week follow-up 51% of those setting a quit date had successfully quit. Prescribing of nicotine replacement therapy (NRT) has increased markedly since April 2001 when all forms of NRT became available on FP10 prescription. In the quarter to December 2001, there were 240,000 items for NRT costing £5.2 million. Total use of NRT funded by the NHS will be higher because NRT is available through other routes such as voucher schemes. Due to concerns about its adverse effects, prescribing of amfebutamone/bupropion has declined from a peak of 146,000 items in the quarter to March 2001 to under 37,000 items in quarter to December 2001.

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Trends in Spending on Cardiovascular drugs (Chart 2)

Chapter 2 of the NSF specifies two main priorities:

To identify people with clinical evidence of CHD, ischaemic stroke, transient ischaemic attack or peripheral vascular disease and offer them comprehensive advice and appropriate treatment to reduce their risks.
To identify people without diagnosed CHD or other occlusive arterial disease but whose risk of CHD events is greater than 30% over 10 years.

There are a variety of tools for risk assessment. The Joint British Societies Coronary Risk Prediction Chart (available in the BNF) is easy to use and provides a good balance of accuracy. Whichever tool is chosen, they all have limitations in some patient groups².

Information about modifiable risk factors (smoking, physical activity, diet, alcohol consumption, weight and diabetes) should be provided to people identified under priorities 1 and 2. Drug treatment is targeted at the individual's risk factors (e.g. statins for hyperlipidaemia) and pre-existing conditions (e.g. beta blockers for people who have had a myocardial infarction).

Lipid regulating drugs
Statins and dietary advice to lower cholesterol below 5.0 mmol/l or to reduce total serum cholesterol by 20-25%, whichever would result in the lowest level should be offered to people at high risk of CHD. Equivalent figures for LDL cholesterol are to below 3 mmol/l or by 30%. Prescribing of statins has increased by nearly 5-fold in the last 5 years to 3.5 million items in the quarter to December 2001 at a cost of £119.6 million. Simvastatin is the most frequently prescribed statin followed by atorvastatin (1.5 million and 1.3 million items quarter to December 2001 respectively). Preliminary data from the Heart Protection Study (not yet published) suggest that simvastatin reduces major vascular events in women, the elderly and people with average or below average cholesterol levels³. However the priorities for statin use set out in the NSF are unlikely to change as a result of this trial.

Antihypertensive drugs
Prescribing of antihypertensive drugs continues to increase. In the quarter to December 2001 there were 7.8 million items for diuretics, 5.4 million items for beta blockers and 4.4 million items for calcium channel blockers. This represents increases of 35%, 48% and 34% over the last 5 years respectively. In the same period the number of items for drugs affecting the renin angiotensin system doubled to 5.7 million per quarter. These drug groups all have indications other than hypertension therefore some of the increased prescribing will be for other conditions. The highest costs are for drugs affecting the renin angiotensin system (£88.9 million quarter to December 2001) and calcium channel blockers (£71.5 million). Diuretics (£15.8 million) and beta blockers (£21.7 million) cost a lot less.

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Cost For 28 Days Treatment

Use of thiazide diuretics has almost doubled in the last 5 years to 3.8 million items in the quarter to December 2001. However the cost of thiazide diuretics has increased over 4-fold to £5.3 million. 93% of thiazide diuretic items are for bendrofluazide (77% of cost). Atenolol is the most commonly prescribed beta blocker (3.5 million items, £5.3 million quarter to December 2001). Nearly as much is spent on bisoprolol (£4.8 million) but there are a lot fewer items than for atenolol (359,000). ACE inhibitors account for 82% of all items for renin angiotensin system drugs (4.6 million items quarter to December 2001) and 70% of costs (£61.8 million). The most frequently prescribed ACE inhibitors are lisinopril (1.5 million items, £21.6 million) and ramipril (1.1 million items, £15.9 million). Losartan is the most frequently prescribed angiotensin II receptor antagonist (369,000 items at £11.3 million quarter to December 2001).

There is no clear evidence that any drug prescribed solely for hypertension (i.e. excluding people with other indications such as heart failure, stroke or myocardial infarction) consistently produces better cardiovascular outcomes over alternative drugs. Combinations of two or more drugs are often required to maintain blood pressure below 140/85 mmHg. Co-morbidities and contraindications will influence choice of initial therapy, however a thiazide diuretic or a beta blocker is cost-effective in many patients. There is now evidence that lowering blood pressure is beneficial in patients with previous stroke or TIA, however it is not clear whether any particular drug class offers greater benefits4. For patients who have had a myocardial infarction the NSF recommends a beta blocker (whether or not hypertension is also present). For people who have left ventricular dysfunction, an ACE inhibitor is recommended.

The recent LIFE study showed that in a selected group of patients with hypertension and left ventricular hypertrophy, patients on losartan experienced the primary composite end point of cardiovascular death, myocardial infarction and stroke significantly less often than patients on atenolol⁵. The number needed to treat (NNT) for this end point is 56. Exclusions from LIFE included recent myocardial infarction or stroke; heart failure; and angina requiring treatment with beta blockers or calcium channel blockers. The results of this study are therefore not directly applicable to many of the high priority patients identified for treatment in the NSF.

Antiplatelet drugs
Among patients at high risk of occlusive vascular events antiplatelet therapy reduces the relative risk of any serious vascular event by about one quarter⁶. The NSF only recommends low dose aspirin for patients with diagnosed CHD or other occlusive arterial disease. Whether the benefits of aspirin outweigh its risks in people without symptoms of cardiovascular disease is still uncertain1. Prescribing of antiplatelet drugs has doubled in the last 5 years reaching 5.1 million items for the quarter to December 2001. At the same time their cost has increased 10-fold to £15.9 million. Aspirin is by far the most frequently prescribed antiplatelet drug (91% of items and 25% of cost, quarter to December 2001). Clopidogrel is used much less frequently (4% of items) but it accounts for 57% of antiplatelet cost.

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Variation between Health Authorities in Spending on Antiplatelet drugs (Quarter to December 2001) (Chart 3)

There is a 3-fold variation in total spending (NIC/1,000 PUs) on antiplatelet drugs across health authorities, whilst spending on clopidogrel shows a 5-fold variation (chart 3). Health authorities spending the most on antiplatelet drugs are nearly all in the North and have high rates of CHD. Aspirin is the most cost effective antiplatelet drug to reduce the risk of vascular events in high risk patients. Clopidogrel appears to be a safe and effective alternative but there is substantial uncertainty about the size of any additional benefit compared to aspirin⁷. In patients with acute coronary syndrome without ST-segment elevation, clopidogrel plus aspirin for up to 12 months was more effective in preventing a combined outcome of cardiovascular death, non-fatal myocardial infarction and stroke than aspirin alone (NNT 48)⁸. However evidence of benefit from using clopidogrel plus aspirin in patients with stable angina is lacking and because of the risk of bleeding it should not be used in these people (who are at lower risk of a cardiovascular event).

More information about the NSF can be found by clicking here

References

Murphy M et al. Cardiovascular disorders Primary prevention. Clin Evid 2001; 6: 82-113
National Prescribing Centre. Assessing cardiovascular risk (part 2). MeReC Bulletin 2000; 11: 29-32
www.ctsu.ox.ac.uk/~hps/
National Prescribing Centre. Secondary prevention of stroke: what does the PROGRESS trial add? MeReC Extra 2001; issue3
Dahlof B et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995-1003
Antithrombotic Triallists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324: 71-86
C. Sudlow. Cardiovascular disorders Secondary prevention of ischaemic cardiac events. Clin Evid 2001; 6: 117-119
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494-502

Summary

Key interventions to prevent CHD at the population level are:
reducing smoking; promoting healthy eating; promoting physical activity and reducing overweight and obesity
The highest priorities for statin use are people with established CHD and people whose risk of a CHD event is greater than 30% over 10 years
There is no clear evidence that any class of antihypertensive drug consistently produce better cardiovascular outcomes
Lowering blood pressure is beneficial in patients with previous stroke or TIA
Aspirin is the most cost effective antiplatelet agent to reduce the risk of vascular events in high risk patients